Autophagy in Microglia-mediated De- and Re-myelination

• Applicant: Professor Dr. Jan Lünemann
• Subject Area: Experimental Models for the Understanding of Nervous System Diseases ; Immunology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 458695329

While phagocytosis and the regulation of inflammatory responses are key functions of microglia to maintain CNS homeostasis and crucially contribute to CNS immune pathologies, mechanisms that govern these functions are poorly understood. The degradative pathway of autophagy has fundamental roles in immunity and immune-related functions of conserved autophagy proteins also occur independently of autophagosome formation. One of such emerging non-canonical pathways is LC3-associated phagocytosis (LAP) that requires many of the same proteins as conventional autophagy but, instead of intracellular constituents, degrades extracellular material that engages receptor signaling after apoptotic cell recognition or through pattern recognition receptors. Here, we hypothesize that autophagy proteins in microglial cells are required to maintain CNS integrity during senescence and support remyelination upon CNS injury. We will genetically dissect the autophagy machinery in microglial cells in vivo and determine its functions during ageing and in animal models related to demyelinating diseases such as multiple sclerosis (MS). We hope that our research program will provide new mechanistic concepts on microglia immune functions during health and disease with the long-term goal to identify new therapeutic strategies for the benefit of people suffering of chronic demyelinating CNS diseases such as MS.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Marco Prinz